November 11, 2013

Not All Fears Are Created Equally – Or In The Same Place

Fear is generated in different parts of the brain depending on the source of the fear. We learned this based on work conducted at the Cornelius Gross laboratory at the European Molecular Biology Laboratory (EMBL) in Monterotondo, Italy. The study, published in today’s Nature Neuroscience, highlights how – at least in mice – fears are processed by different sets of neurons depending on the type of external stimuli encountered.

According to Bianca Silva, pre-doctoral research scientist at EMBL, “We found that there seems to be a circuit for handling fear of predators – which has been described anatomically as a kind of defense circuit – but fear of the same species uses the reproductive circuit instead.” Silva continues, “Fear of pain goes through yet another part of the brain.”

For the study, Silva presented the subject mice with three unique kinds of threats: a particularly aggressive mouse; a predator in the form of a rat; and a mild electric shock to the feet. Regardless of which threat the mouse encountered, the behaviors were exactly as expected. The mouse chose either to run or freeze. However, the activity in their brains was generated in different areas depending on which threat the creature encountered.

The part of the brain responsible for signaling a threat is called the ventromedial hypothalamus (VMH). When presented with the aggressive mouse or the predator rat, brain activity in this region lit up, but not in the same way. Fear of the aggressive mouse activated neurons in the bottom and sides of the VMH. The predator rat generated neural activity in the VMHs central and upper areas.

To confirm this, Silva and colleagues used drugs that block the neurons in the ‘rat fear’ areas: the subject mouse was no longer afraid of the rat, but still exhibited a fear response when the other aggressive mouse was introduced. This, say researchers, shows the mouse needs the VMHs central and upper areas to process fear of predators.

It’s all well and good for scientists to probe the brains of mice, but what could this mean for humans? It turns out the human brain, with similar circuitry, behaves in a similar manner. While the ‘fight or flight’ response is experienced from fear, we, like the mouse, experience different kinds of fear. Understanding this difference, say the researchers, could lead to better and more efficient treatments for humans who exhibit specific phobias or panic attacks. Like the drugs administered to the mouse above, pharmaceutical therapies could be developed that target only the relevant region of the brain. This, says Cornelius Gross who coordinated the study, is not an end of their research but rather a beginning.

“What we’re interested in, in the long-run, is if these results represent a kind of mental state. If so, mice should be able to be in that state without expressing it in their behavior – do they re-live that fear, for example? These are not easy questions to ask in a mouse, but we’re looking into them.”

Additionally, Gross’ lab wants to explore the evolution of these fears along with the neural circuitry that processes them. Working in partnership with the Gross lab, a separate team under the direction of Detlev Arendt at EMBL Heidelberg has found a similar brain region in a marine worm. This is especially interesting because Arendt’s team believes the worm closely resembles our ancestors from 600 million years ago. If the team is correct, then it is possible they may have discovered the ancestral fear circuit that has traversed time and species and made it all the way to the modern day Homo sapien brain.

The study is being presented today and Wednesday at this year’s Society for Neuroscience Neuroscience 2013 conference.